This project seeks to determine the role of oxidation of proteins and peroxidation of lipids in demyelination and to refine and test a hypothesis that lipid peroxidation and reactive oxygen intermediates are involved in the pathogenesis of demyelinating diseases. During FY 1988, studies submitted for publication have shown that prominent white matter lesions develop in mongolian gerbils treated with 100% normobaric oxygen for three hours following fifteen minutes of bilateral carotid occlusion. Specifically, this study showed that selective myelin damage occurred in lesions of the striatum, thalamus, mesencephalon and posterior limb of the internal capsule in oxygen-treated gerbils. Relative preservation of axons was seen within these lesions. On the other hand, less damage to cortical neurons was seen in the animals treated with oxygen. Earlier studies of Mongolian gerbils treated with oxygen following global brain ischemia (Mickel HS, et al. 1987), demonstrated increased lipid peroxidation and increased fourteen day cumulative mortality.